study of a pd vwf/fviii, biostate®, in subjects with haemophilia a

Conditions: Hemophilia A

Summary: the aim of this study are to * assess the efficacy of biostate® \[study product (sp)\] in subjects with haemophilia a * compare the pharmacokinetics of biostate® \[sp\] with the previously marketed product biostate® (here referred to as biostate® \[reference product (rp)\]). this study is divided into 3 parts: part 1: cross-over pharmacokinetic (pk) component. pk subjects will be randomised to determine the order in which they receive the two study products. this part of the study is double-blinded. part 2: efficacy component. all subjects will receive biostate® \[sp\] as required to manage their haemophilia condition for an estimated period of 6 months (or minimum of 50 exposure days) to assess efficacy and safety of the product. this part of the study is open-label. part 3: repeat pharmacokinetic assessment. subjects who participated in part 1 (pk component) will undergo a repeat pk assessment on day 180 following administration of biostate® \[sp\].


Eligibility criteria:
inclusion criteria: * diagnosed with haemophilia a with ≤ 1% factor viii (fviii) levels in the absence of factor replacement * evidence of vaccination against hepatitis a and b (or presence of antibodies against hepatitis a and b due to either a previous infection or prior immunisation) within 10 years prior to day 1 documented in the medical notes * at least 150 days of prior exposure to a fviii replacement product * written informed consent given exclusion criteria (for participation in the pharmacokinetic (pk) component): * active bleeding * body weight \> 100 kg exclusion criteria (for all subjects): * receipt of an infusion of any fviii product, cryoprecipitate, whole blood, plasma, or desmopressin acetate (ddavp) in the 4 days prior to day 1 * known history of fviii inhibitors, or fviii inhibitor level \> 0.6 bethesda units (bu) at screening * receipt of aspirin or other non-steroidal anti-inflammatory drugs (nsaids) within 7 days of administration of study product. * cd4 lymphocytes \< 200/µl. subjects wo are hiv-1 positive may be considered for the study if viral load ≤ 200 particles/µl at screening and all other eligibility criteria are met. * impaired liver function ie. bilirubin \>1.5 x upper limit of normal (uln) and/or ast/alt \> 2.5 x uln at screening. * acute or chronic medical condition, other than haemophilia a, which may, in the opinion of the investigator, affect the conduct of the study * von willebrand disease (vwd) with von willebrand factor:ristocetin cofactor (vwf:rco) level \< 50 iu/dl at screening * evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit * known or suspected hypersensitivity or previous evidence of severe side effects to biostate®, fviii concentrates or human albumin * participation in a clinical study or use of an investigational compound (e.g. a new chemical entity not approved for clinical use) in the 3 months preceding the first day of study drug administration, or plans to enter such a study during the study period * not willing and/or not able to comply with study requirements

Keywords: hemophilia a